Clinical Research Directory

Allogeneic Hematopoietic Stem Cell Transplant for GATA2 Mutations

Background: \- GATA2 deficiency is a disease caused by mutations in the GATA2 gene. It can cause different types of leukemia and other diseases. Researchers want to see if a stem cell transplant can be used to treat this condition. A stem cell transplant will give stem cells from a matching donor (related or unrelated) to a recipient. It will allow the donor stem cells to produce healthy bone marrow and blood cells that will attack the recipient s cancer cells. Objectives: \- To see if stem cell transplants are successful at treating GATA2 mutations and related conditions. Eligibility: \- Recipients who are between 6 and 70 years of age and have GATA2 deficiency. Design: * All participants will be screened with a physical exam and medical history. Blood samples will be collected. Recipients will have imaging studies and other tests. * Recipients will have chemotherapy or radiation to prepare for the transplant. On the day of the transplant, they will receive the donated stem cells. * Recipients will stay in the hospital until their condition is stable after transplant. * Frequent blood tests and scans will be required for the first 6 months after the transplant, followed by less frequent visits over time.

Genetic Analysis of Immune Disorders

The purposes of this study are to 1) identify the genes responsible for certain immune disorders, 2) learn about the medical problems they cause, and 3) learn how to predict who is likely to develop these disorders and what the risk is of passing them on to children. The immune system is the body s defense system. Some immune deficiencies impair a person s ability to fight infections; others render a person susceptible to allergies, or to autoimmune diseases such as lupus or arthritis, in which the immune cells (white blood cells) attack and destroy the body s own tissues. Patients with immune disorders known or suspected to have a genetic basis and their family members may enroll in this study. Eligibility will be determined by a review of the patient s medical records and family medical history. Participants will provide a small blood sample for genetic (DNA) and white blood cell analysis. Gene samples (but not white blood cells) may also be obtained by mouth brushing or skin biopsy. For the mouth brushing, a small brush is rubbed against the inside of the cheeks for 1 minute to wipe off some cells. For the skin biopsy, a small circle of skin (about 1/8 inch) is removed under local anesthetic. Pregnant women may be asked to provide a fetal sample (amniotic fluid cells or chorionic villus sample). All samples will be used for immune or genetic studies of the family s immune disorder. If test results show a specific genetic variation responsible for the family s immune disorder, a report will be sent to the patient s doctor or genetic counselor, who will discuss the implications for the family. NIH researchers and genetic counselors will also be available to explain results and answer questions. Information will not be available in the case of disorders that cannot yet be linked to a specific genetic abnormality. Information from this study will increase knowledge about the immune system and what causes immune deficiencies. Participants may also learn the underlying cause of an immune disorder that affects them or someone in their family information may be useful in guiding treatment and in making decisions regarding family planning.

A Phase II Study of Allogeneic Hematopoietic Stem Cell Transplant for Subjects With VEXAS (Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic) Syndrome

Background: Allogeneic hematopoietic stem cell transplant involves taking blood stem cells from a donor and giving them to a recipient. The transplants are used to treat certain diseases and cancers. Researchers want to see if the transplant can treat VEXAS Syndrome. Objective: To see if stem cell transplants can be successfully performed in people with VEXAS and even improve the disease. Eligibility: People ages 18-75 who have VEXAS Syndrome that has caused significant health problems and standard treatment either has not worked or is not available. Design: Participants will be screened with: Physical exam Medical review Blood and urine tests Heart and lung function tests Bone marrow biopsy Participants will have a chest x-ray. They will have an imaging scan of the head, chest, abdomen, pelvis, and sinus. They will have a bone density scan. They will have a dental exam and eye exam. They will meet with specialists. They will repeat some screening tests. Participants will be admitted to the NIH hospital. They have a central venous catheter put into a vein in the chest or neck. They will receive drugs to prepare their bone marrow for the transplant. They may have total body irradiation. They will receive the donor stem cells through the catheter. They will get other drugs to prevent complications and infections. After discharge, they must stay in the DC area for 3 months for weekly study visits. Participants will have study visits 30, 60, 100, 180, 210, 240, 300, and 360 days later. After that, they will have yearly visits for 2 years and then be contacted yearly by phone....

OPtimisation of Antiviral Therapy in Immunocompromised COVID-19 Patients: a Randomized Factorial Controlled Strategy Trial

The overall purpose of the trial is to evaluate the efficacy and safety of possible combination antiviral therapy DAA (remdesivir + nirmatrelvir/r)∞ versus the reference monotherapy (nirmatrelvir/r alone) and to assess the efficacy and safety of increasing the nirmatrelvir/r course from 5- to 10 days in immunocompromised patients diagnosed with asymptomatic or mild to moderate COVID-19.

OPtimisation of Antiviral Therapy in Immunocompromised COVID-19 Patients

The overall purpose of the trial is to evaluate the efficacy and safety of possible combination antiviral therapy direct antiviral agents (remdesivir + nirmatrelvir/r) versus the reference monotherapy (nirmatrelvir/r alone) and to assess the efficacy and safety of increasing the nirmatrelvir/r course from 5- to 10 days in immunocompromised patients diagnosed with asymptomatic or mild to moderate Coronavirus Disease 2019 (COVID-19).

Impact of a Strategy Based on Bacterial DNA Detection to Optimize Antibiotics in Immunocompromised Patients With Hospital-acquired Pneumonia Requiring Mechanical Ventilation

RESPIRE is a randomized, unblinded, controlled study to measure the impact of a strategy based on a PCR test on the adjustment of antimicrobial therapy in immunocompromised patients suspected with ventilator-associated or hospital-acquired pneumonia (VAP/HAP) requiring mechanical ventilation (MV) in Intensive Care Unit (ICU). The gold-standard microbiological diagnostic method for pneumonia in the ICU is based on culture identification and antimicrobial susceptibility testing. Results are obtained in several days after the initiation of empiric antimicrobial therapy, exposing patients to a potential inappropriate broad-spectrum antimicrobial treatment. We aim to measure the impact of a PCR-based strategy to improve the percentage of patients with VAP or HAP receiving targeted antimicrobial therapy 24 hours after diagnosis compared to standard care

Clozapine-related Immunodeficiency in Parkinsons Disease

Clozapine is a second generation antipsychotic drug used in psychiatry to treat schizophrenia, affective disorders or certain symptoms of dementia. In neurology, clozapine is frequently used and recommended to manage symptoms of psychosis associated with Parkinson's disease (PD). The risk of neutropenia or agranulocytosis associated with clozapine estimated at 1.3% is well known to doctors around the world with a peak at one month and a decrease in risk after more than a year of treatment. This risk has led to the policy of "no blood, no drugs" and monitoring of the complete blood count (CBC) weekly for 18 weeks and then monthly for the duration of treatment. Some studies suggest an increased risk of infections related to immunodeficiency induced by clozapine itself. This clozapine-induced immunodeficiency would be comparable to that encountered in patients with common variable immunodeficiency or under immunosuppressive treatment. In addition, this immunosuppressive effect linked to clozapine would not be dose dependent but time dependent. However, the only studies currently performed have been in psychiatric patients treated for schizophrenia. It seems important to specifically explore clozapine-related immunodeficiency in PD patients treated with clozapine for PD-related psychosis. In this study, the investigators propose to evaluate the variations in serum immunoglobulin levels and lymphocyte subpopulations (B, T, NK) in parkinsonian patients treated with Clozapine at 6 months and 1 year after initiation of treatment.

Allogeneic Hematopoietic Stem Cell Transplantation With Briquilimab-Based Conditioning in Participants With GATA2 Deficiency

Background: People with GATA2 deficiency have a mutation on the GATA2 gene. This gene affects immune function. People with this disease are prone to serious infections; in time, they may develop blood cancers. A hematopoietic stem cell (HSC) transplant can cure GATA2 deficiency, but using stem cells donated by other people can cause serious side effects. Objective: To test a new drug (Briquilimab) to see if it can make HSC transplants safer. Eligibility: People aged 6 to 70 years who have GATA2 deficiency. Design: Participants will be screened. They will have a physical exam, with blood and urine tests. They will have tests of their heart and lung function. They may have a bone marrow biopsy: Their hip will be numbed; a large needle will be inserted to draw out tissue from inside the pelvis. Participants will have a central venous catheter placed in a vein of the neck or chest. This will be used to draw blood and administer drugs. Briquilimab will be given through the catheter about 11 days before the transplant. This is part of conditioning: preparing the body to receive the new stem cells. Conditioning also includes other medications and total body irradiation. Donor stem cells will be administered through the catheter. Participants will receive other approved drugs to help prevent side effects. Participants will stay in the hospital from the beginning of the conditioning until several weeks after the transplant. They will remain in the local area for 100 days after discharge; they will come to the clinic at least once a week during this time. Follow-up visits will continue for 3 years....

Vaccine-induced Immunity in Immunocompromised Patients

Managing respiratory virus infections in immunocompromised patients requires a multidisciplinary approach, including vaccination, though its effectiveness is often suboptimal in these individuals. In hematological patients, poor humoral immunogenicity is common, especially when the B cell axis is affected by disease or treatment, while T cell responses may offer better protection. Current immunologic data on these patients is limited, focusing mostly on serologic parameters. To address this, we will conduct an observational study analyzing early and late booster vaccinations, with a focus on virus-specific T cell responses in vaccinated patients.

Phase 1/2: CD45RA Depleted Stem Cell Addback to Prevent Viral or Fungal Infections Post TCRab/CD19 Depleted HSCT

The major morbidities of allogeneic hematopoietic stem cell transplant (HSCT) using donors that are not human leukocyte antigen (HLA) matched siblings are graft vs host disease (GVHD) and life- threatening infections. T cell receptor alpha beta (TCRαβ) T lymphocyte depletion and CD19+ B lymphocyte depletion of alternative donor hematopoietic stem cell (HSC) grafts is effective in preventing GVHD, but immune reconstitution may be delayed, increasing the risk of infections. The central hypothesis of this study is that an addback of CD45RO memory T lymphocytes, derived from a fraction of the original donor peripheral stem cell product depleted of CD45RA naïve T lymphocytes, will accelerate immune reconstitution and help decrease the risk of infections in TCRab/CD19 depleted PSCT.

SYSTEMS-LEVEL ANALYSES OF IMMUNE DYSREGULATION

The aim of the SAID study is to create a national resource in Sweden to enable comprehensive immunological analyses of an extremely complex and clinically challenging group of individuals with variable forms of immune system dysregulation. We hope to establish a biobank of primarily blood and fecal samples from children and adults, with confirmed or suspected immune dysregulation, as well as age- and sex- matched healthy controls, for comparisons of immune cell/mediator alongside various clinical presentations of these immunological diseases as well as microbiome samples as possible a possible modifier of clinical presentations. The project will also include the establishment of a national database with deep immunological data, treatment and clinical outcomes for these patients, accessible to participating researchers and clinicians.